Abstract The introduction of combined antiretroviral therapies has reduced the incidence and severity of HIV-related encephalopathy in youth living with HIV. However, neurodevelopmental delays and cognitive impairment are nonetheless still common in this population. Unfortunately, in resource-limited settings (RLS), where HIV infection impacts millions of children, cognitive and neurodevelopmental disorders commonly go undetected because of a lack of appropriate assessment instruments and local expertise. In this project, we build on the synergistic work of two research groups to: (1) culturally adapt and validate the Penn Computerized Neurocognitive Battery (CNB) and examine its validity for detecting both advanced and subtle neurodevelopmental problems among school-aged HIV-infected and HIV-exposed children in RLS; and (2) simultaneously fine-tune a brief screening instrument (The Pediatric Symptom Checklist, PSC) to prioritize children most likely to benefit from further cognitive assessments. The CNB is a well-validated battery of neurocognitive tests that assesses all major domains of cognitive functioning in adults and children as young as 5 years of age. It has shown sensitivity to mild cognitive deficits, and has been applied in large-scale studies and in multiple cultural contexts. We aim to validate the CNB in youth in Botswana, a RLS with high rates of perinatal exposure to HIV and limited neurocognitive assessment tools and expertise, by culturally adapting and then administering the adapted version of the CNB to 200 HIV-infected, 200 HIV-exposed uninfected, and 240 HIV-unexposed uninfected children. A series of analyses will be conducted to examine the reliability and construct validity of the CNB in these populations. Since a one hour comprehensive cognitive assessment may not be feasible to implement among all children in many busy clinics in resource-limited settings, we will also adapt a rapid psychosocial screening tool, the Pediatric Symptom Checklist to make it suitable for identifying children who are most likely to benefit from further neurocognitive assessment. To accomplish these aims, we have assembled a unique, multi-disciplinary expert team with long-term experience developing and validating novel and highly adaptable neurocognitive assessments, and conducting Africa-based collaborative HIV research. This project will apply procedures for effective translation and cultural adaptation that have been developed through extensive collaborations of our group with international researchers from both Western and non-Western cultures (e.g., in South Africa in an adult Xhosa-speaking population). If successful, the proposed tools would provide practical screening and streamlined, comprehensive assessments that could be widely used in RLS to identify children with cognitive deficits within programs focused on the care and treatment of children living with or affected by HIV. The utility of such assessments could extend well beyond children affected by HIV and increase general access to pediatric cognitive assessments in RLS.